There is at present no readily available experimental system in which human cancer cells can be grown in the context of a mixed population of normal differentiated human cells. Such an experimental system would be advantageous for investigating responses to anticancer therapies and for exploring biological aspects of cancer cell growth (e.g. tumor cell invasion, angiogenesis, proliferation, migration and metastasis among others). Pluripotent human embryonic stem cells (hESC) are capable of differentiating into many distinct normal cell types, which makes them and their derivatives suitable candidates for research and medical applications.
U.S. Pat. No. 5,690,926 discloses non-murine pluripotential cells, including human pluripotential cells, that have the ability to be passaged in vitro for at least 20 passages and which differentiate in culture into a variety of tissues.
EP Patent No. 380646 discloses to the use of leukaemia inhibitory factor (LIF), in the isolation and propagation of embryonic stem cells in vitro.
U.S. Pat. No. 5,453,357 discloses a non-mouse pluripotential embryonic stem cell which can: (a) be maintained on feeder layers for at least 20 passages; and (b) give rise to embryoid bodies and multiple differentiated cell phenotypes in monolayer culture. The invention further provides a method of making a pluripotential embryonic stem cell comprising administering a growth enhancing amount of basic fibroblast growth factor, leukemia inhibitory factor, membrane associated steel factor, and soluble steel factor to primordial germ cells under cell growth conditions, thereby making a pluripotential embryonic stem cell.
U.S. Pat. No. 5,753,506 discloses a method of screening factors for the ability to promote the formation of embryonic stem cells, comprising combining primordial germ cells with a factor selected from the group consisting of fibroblast growth factor, leukemia inhibitory factor, membrane associated steel factor, and soluble steel factor with the factor to be screened and determining the formation of embryonic stem cells, whereas the formation of embryonic stem cells indicates a factor capable of promoting the formation of embryonic stem cells.
A method of enriching a population of mammalian cells for stem cells is disclosed in U.S. Pat. No. 6,146,888. The method comprises the steps of: providing in vitro a mixed population of mammalian cells whose genome comprises at least one nucleic acid construct encoding an antibiotic resistance gene operatively linked to a promoter which preferentially expresses said antibiotic gene in mammalian stem cells.
A method for culturing human embryonic stem cells in vitro for prolonged maintenance while preserving the pluripotent character of these cells, as well as a purified preparation of said cells, is disclosed in U.S. Pat. No. 6,200,806. It is further disclosed that these embryonic stem cells also retain the ability, throughout the culture and after continuous culture for eleven months, to differentiate into all tissues derived from all three embryonic germ layers.
A method for selective ex-vivo expansion of stem cells is disclosed in U.S. Pat. No. 6,479,261. The method comprises the steps of separating stem cells from other cells and culturing the separated stem cells in a growth media comprising a modified human interleukin-3 polypeptide having at least three times greater cell proliferative activity than native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation and methylcellulose assay.
A method of inducing angiogenesis in a tissue of a mammal, comprising the step of implanting a microorgan within the tissue of the mammal, is disclosed in International Publication No. WO 01/00859. The microorgan is derived from said mammal or from another mammal, wherein the organ may be selected from the group consisting of a lung, a liver, a kidney, a muscle, a spleen, a skin and a heart.
A genetically modified micro-organ explant expressing at least one recombinant gene product and methods for generating thereof, wherein the micro-organ explant comprises a population of cells and maintains a microarchitecture of an organ from which it is derived and at the same time having dimensions selected so as to allow diffusion of adequate nutrients and gases to cells in the micro-organ explant is disclosed in International Publication No. WO 03/035851
A population of hESC which under appropriate culture conditions differentiate into a substantially high percentage of insulin producing cells in spontaneously formed aggregated embryoid bodies is disclosed in International Publication No. WO02/092756 which is assigned to the applicant of the present invention.
Partially committed progenitors derived from embryonic stem cells that express telomerase and not being terminally differentiated and hence are capable of continued proliferation, are disclosed in International Publication No. WO 03/066839 which is assigned to the applicant of the present invention.
Nowhere in the background art is it taught or suggested that a multicellular compositions comprising human embryonic stem cells and cancer cells of human origin may be cocultured and moreover useful for drug screening.